Propagation zone configuration of many known bioreactors imposes constraints on cell growth. For example, conventional hollow fiber bioreactors comprise an intracapillary space (ICS) and an extracapillary space (ECS). Cells are seeded in the ECS for cell growth and production of cell-expressed biomolecules. The cells in the ECS are nourished by nutrients which diffuse across the hollow fiber membrane from media circulated through the ICS. The various disadvantages of conventional hollow fiber bioreactors include:
(1) The growth rate of cells seeded in the ECS is slower than that in static T-flask culture or in the stirred tank system.
(2) Cell masses are immobilized in the hollow fiber bundles with consequent resistance to nutrient diffusability and lower cell viability.
(3) The harvest of cell-expressed biomolecules is limited with consequent lower volumetric biomolecule productivity.
(4) Scale-up of hollow fiber bioreactors implicates complex flow paths because the efficiency of such systems is proportional to the surface area of the hollow fiber membrane and the ratio of the total ICS to the total ECS.